Barriers to prescribing proprotein convertase subtilisin-kexin type 9 inhibitors after coronary revascularisation.

BACKGROUND: Guidelines advocate for intensive lipid-lowering in patients with atherosclerotic cardiovascular disease (ASCVD). In May 2020, evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, became government subsidised in Australia for patients with ASCVD requiring further low-density lipoprotein cholesterol (LDL-C) lowering. AIM: To identify barriers to prescribing PCSK9 inhibitors in hospitalised patients with ASCVD. METHODS: A retrospective 3-month, single-site, observational analysis was conducted in consecutive patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Lipid-lowering therapy prescriptions, including PSCK9 inhibitors, were assessed using electronic medical records, compared against the Australian Pharmaceutical Benefits eligibility criteria, and barriers to PCSK9 inhibitor use identified. RESULTS: Of 331 patients, 244 (73.7%) underwent PCI and 87 (26.3%) underwent CABG surgery. A lipid profile during or within 8 weeks of admission was measured for 202 (82.8%) patients undergoing PCI and 59 (67.8%) undergoing CABG surgery. In patients taking high-intensity statins on admission (n = 109), LDL-C ≥1.4, ≥1.8 and >2.6mmol/L was seen in 64 (58.7%), 44 (40.4%) and 19 (17.4%) patients respectively. High-intensity statin prescribing at discharge was high (>80%); however, ezetimibe was initiated in zero patients with LDL-C ≥1.4 mmol/L. There was variable advice given by clinicians for LDL-C targets. No patients met the criteria for subsidised PSCK9 inhibitor therapy, largely due to lack of qualifying lipid levels following combined statin and ezetimibe therapy. CONCLUSION: Prescribing of non-statin LDL-C-lowering therapies remains low in patients with ASCVD. Underprescribing of ezetimibe and suboptimal lipid testing rates are barriers to accessing subsidised PCSK9i therapy using current Australian eligibility criteria.

Investigating the effect of an education programme on diabetes and lipid lowering medication usage following coronary artery bypass graft surgery.

BACKGROUND: Guidelines advocate multifactorial cardiovascular risk management in patients with diabetes and atherosclerotic cardiovascular disease. AIM: In hospitalised patients with diabetes following coronary artery bypass graft (CABG), we aimed to evaluate the impacts of decision-support algorithms for optimising glycaemia and lipid-lowering. We also assessed the safety of initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors near time of hospital discharge. METHODS: This was a single-site, pre- and post-intervention analysis of glucose and lipid management in consecutive hospitalised patients with diabetes undergoing CABG surgery. The intervention involved education and decision-support algorithms designed by a multidisciplinary committee to guide cardiac surgery unit clinicians. RESULTS: A total of 200 patients were included in the study. The pre- and post-intervention groups had similar baseline characteristics (HbA1c 7.9 ± 1.9% vs 8.1 ± 1.8%). Of 4092 blood glucose measurements, the incidence of levels between 5 and 10 mmol/L was not different post-intervention (55.5% vs 57.0%; P = 0.441). Fewer endocrinology consultations occurred (59.0% vs 45.0%; P = 0.048) and rates of hypoglycaemia remained low. High-intensity statin was prescribed in >90% pre- and post-intervention, although non-statin lipid-lowering agents remained <10% despite patients not achieving LDL-C targets. No 30-day readmissions for diabetic ketoacidosis occurred in patients prescribed SGLT2 inhibitors. CONCLUSION: The intervention did not improve inpatient glycaemia or increase non-statin lipid-lowering prescriptions in patients with diabetes following CABG surgery but did reduce reliance on specialty input. Initiation of SGLT2 inhibitor therapy near time of hospital discharge was not associated with safety concerns. Alternative interventions or strategies are required to optimise glycaemia and non-statin lipid-lowering therapy prescribing in this setting.

A prospective six-month audit of inpatient hypoglycemia in step-down general medical and geriatric wards.

This study aimed to assess the incidence and associates of hypoglycemia in patients transferred after stabilization on an Acute Medical Unit to two general medical or two geriatric wards at an urban Australian hospital. In a six-month audit representing 20,284 patient-days of observation, 59 inpatients experienced hypoglycaemia (blood glucose ≤3.9 mmol/L) during 65 hospitalizations. Inpatients experiencing hypoglycemia accounted for 7.2% of all inpatient bed-days, a figure that was greater for general medical (9.2% of bed-days) compared with geriatric (6.0% of bed-days) wards (P<0.001). Inpatient hypoglycemia often had no precipitant such as a missed/delayed meal, occurred disproportionately at night (41% of episodes), was severe (blood glucose ≤3.0 mmol/L) in one-third of cases, and appeared more frequent in patients with psychiatric/cognitive issues. These data highlight the ongoing issue of hypoglycemia in relatively stable inpatients in an era of blood glucose-lowering therapies associated with a low rate of this acute metabolic complication.

Community-based management of complex type 2 diabetes: adaptation of an integrated model of care in a general practice setting.

BACKGROUND: Overburdened hospital clinics can have adverse outcomes. AIMS: To evaluate the effectiveness and patient acceptability of an integrated model of complex type 2 diabetes care delivered in a community-based general practice by upskilled general practitioners (GP) co-located with an endocrinologist and diabetes nurse educator. METHODS: Patients transferred from hospital clinic lists or referred by local GP were assessed in two southern Perth practices. An upskilled GP and endocrinologist developed a management plan which was communicated to the participant's usual GP. Up to two follow-up visits over 6 months ensured that management was acceptable and effective. RESULTS: A total of 464 people with type 2 diabetes (mean ± standard deviation age = 59.3 ± 13.7 years, 52.2% males) was enrolled. Their mean glycated haemoglobin (HbA1c ) was 9.3% (78 mmol/mol) and their mean body mass index 33.7 kg/m2 . Use of injectable blood glucose-lowering therapies increased between the initial and final visit in association with a median HbA1c reduction of 1.2% (13 mmol/mol) which was sustained to 12 months in assessable participants. There were also reductions in blood pressure, and serum low-density lipoprotein cholesterol and triglyceride concentrations. Patient satisfaction with current treatment, time for self-management, time spent in diabetes-related appointments and diabetes knowledge increased significantly. Non-attendance for scheduled appointments was <10%. Local hospital referrals and waiting lists reduced over the study period. CONCLUSIONS: This study confirms the value of integrated community-based care of complex type 2 diabetes which could represent a sustainable solution to overburdened hospital diabetes outpatient clinics.

Managing inpatient hyperglycaemia and initiating sodium-glucose cotransporter 2 inhibitor therapy in the setting of diabetes and acute coronary syndrome.

We previously showed that implementing algorithms for managing diabetes in acute coronary syndrome was associated with improved inpatient glycaemic control and increased sodium-glucose cotransporter 2 (SGLT2) inhibitor prescriptions. The present study performed 1 year later found that inpatient hyperglycaemia had relapsed to pre-intervention rates, although SGLT2 inhibitor prescriptions remained increased. We discuss the challenges of improving inpatient glycaemic control.

Lipoprotein(a) in Patients With Type 2 Diabetes and Premature Coronary Artery Disease in the Coronary Care Unit.

INTRODUCTION: Lipoprotein(a) [Lp(a)] and diabetes are independently associated with premature coronary artery disease (pCAD). However, there is an inverse relationship between Lp(a) concentration and type 2 diabetes (T2D) risk. We examine whether Lp(a) distribution in patients with pCAD differs between those with or without T2D, and whether elevated Lp(a) is associated with pCAD in patients with T2D. METHODS: Lp(a) concentration was measured in consecutive acute coronary syndrome (ACS) patients in two coronary care units (study one: ACS with or without diabetes, study two: ACS and diabetes). Elevated Lp(a) mass concentration was defined as ≥0.5 g/L and pCAD where CAD was diagnosed age <60 years. The association between elevated Lp(a) and pCAD was assessed using logistic regression. RESULTS: Of 449 patients, 233 (51.9%) had pCAD and 278 (61.9%) had T2D. In patients with pCAD, those with T2D had a significantly lower median Lp(a) concentration (0.13 g/L versus 0.27 g/L, p=0.004). In patients with T2D, elevated Lp(a) was significantly associated with pCAD (OR 2.419, 95% CI 1.513-3.867, p<0.001). After adjusting for gender, smoking, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides, elevated Lp(a) remained significantly associated with pCAD (OR 2.895, 95% CI 1.427-5.876, p=0.003) in patients with T2D. CONCLUSIONS: In coronary care patients with pCAD, patients with T2D had lower Lp(a) concentrations than those without T2D. Despite this, elevated Lp(a) remained predictive of pCAD in patients with T2D. Measurement of Lp(a) should be considered in younger adults with T2D to identify who may benefit from earlier preventative therapies to reduce pCAD burden.

Priorities and practicalities of prescribing diabetes medicines with cardiovascular and renal protective effects: an Australian perspective.

Recent cardiovascular safety trials on sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists have demonstrated the significant cardiovascular and renal benefits of these medications. Diabetes organisations have revised their medication guidelines to include a focus on disease outcomes for cardiovascular disease, heart failure and renal disease. This article summarises latest evidence, guideline recommendations and current Australian Pharmaceutical Benefits Scheme requirements.

Dyslipidaemia in adults with type 1 diabetes-when to treat?

Dyslipidaemia is an important modifiable risk factor contributing to the increased risk of atherosclerotic cardiovascular disease in diabetes. However, determining when to initiate statin therapy in young adults with type 1 diabetes mellitus (T1DM) can often be challenging. This is due to a relative paucity of data in this area to guide management and for developing T1DM-specific risk engines. Current recommendations from international guidelines offer differing approaches to cardiovascular risk stratification and management of dyslipidaemia in T1DM. We present a clinical vignette and comment on the use of nontraditional methods of cardiovascular risk stratification. The strategy for managing dyslipidaemia in young T1DM should be individualized, and recommendations from guidelines should serve to inform clinical judgement.

Icosapent ethyl for dyslipidaemia in patients with diabetes and coronary artery disease: Act now to reduce it.

The risk of atherosclerotic cardiovascular disease (ASCVD) can be significantly reduced in patients with diabetes who are undergoing low-density lipoprotein cholesterol-reducing therapies. However, the elevated triglyceride levels seen in diabetic dyslipidaemia can contribute to residual ASCVD risk. Icosapent ethyl (IPE) has recently been shown to substantially reduce major cardiovascular events in high-risk patients with hypertriglyceridaemia who are undergoing statin therapy. In a real-world study of patients with diabetes and acute coronary syndrome (ACS), 17.1% were found to be eligible for treatment with IPE based on Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) criteria. A significant proportion of patients with diabetes and ACS merit receiving IPE therapy, with important implications for evolving clinical practice guidelines and best standard of care.

Associations of Diabetes and Hyperglycaemia with Extent and Outcomes of Acute Burn Injuries.

BACKGROUND: Severe burns may induce hyperglycaemia in the absence of diabetes, but how glucose trajectories relate to burns outcomes is unclear. AIM: To assess incidence of hyperglycaemia following acute burn injury, and associations with diabetes history and length of stay (LOS). METHODS: Retrospective cohort study of adults admitted with acute burns to tertiary centres. Blood glucose level (BGL), hyperglycaemic episodes (BGL ≥ 11.1 mmol/L) and hyperglycaemic days were recorded. Stress hyperglycaemia was defined as BGL ≥ 11.1 mmol/L without a diabetes history. RESULTS: A total of 30 participants had a diabetes history and 260 did not. Participants with known diabetes had higher mean BGLs (9.7 vs. 9.0 mmol/L, p < 0.001), more hyperglycaemic episodes (28.0 vs. 17.2%, p < 0.001) and hyperglycaemic days (51 vs. 21%, p < 0.001), compared to those without diabetes, despite smaller burns (total body surface area 1.0 vs. 14.8%, p < 0.001). Fourteen participants with stress hyperglycaemia had similar BGLs (at admission 10.3 vs. 11.5 mmol/L; during inpatient stay 9.9 vs. 9.8 mmol/L), more severe burns (15.6% vs. 1.0% TBSA) and longer LOS (18 vs. 7 days, p < 0.001) compared to participants with known diabetes. Extent of burns, having NGT nutrition, age, having inpatient BGL monitoring in the setting of diabetes, or having inpatient BGL monitoring in the absence of diabetes were associated with longer LOS. CONCLUSIONS: In participants with known diabetes, small burn injuries were associated with hyperglycaemia. Stress hyperglycaemia can be triggered by major burn injuries, with early and sustained elevation of BGLs. Further research is warranted to improve inpatient management of BGL in patients with acute burn injury.

Obesity in patients without diabetes undergoing coronary artery bypass graft surgery: Time to select patients for semaglutide.

Patients undergoing coronary artery bypass graft (CABG) surgery require intensive secondary prevention. Semaglutide reduced cardiovascular events in patients with cardiovascular disease and overweight or obesity but without diabetes in the SELECT trial. In this real-world study of 1386 patients without diabetes undergoing CABG surgery in an Australian hospital, approximately 1 in 2 patients (53.3 %) were potentially eligible for semaglutide based on the SELECT trial criteria. These findings highlight that a significant percentage of this very high-risk cohort merit receiving semaglutide for weight management and cardiovascular risk reduction. The implications for optimal care, healthcare costs and clinical guidelines require further evaluation.

Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and the importance of resistance exercise to preserve muscle. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Liraglutide and semaglutide (GLP-1RA), tirzepatide (GLP-1 and GIP receptor dual agonist), and retatrutide (GLP-1, GIP, and glucagon receptor triple agonist) are peptides with incretin agonist activity that induce ∼15-24% weight loss in adults with overweight and obesity, alongside beneficial impacts on blood pressure, cholesterol, blood glucose, and insulin. However, these agents also cause rapid and significant loss of lean mass (∼10% or ∼6 kg), comparable to a decade or more of aging. Maintaining muscle mass and function as humans age is crucial to avoiding sarcopenia and frailty, which are strongly linked to morbidity and mortality. Studies indicate that supervised resistance exercise training interventions with a duration >10 weeks can elicit large increases in lean mass (∼3 kg) and strength (∼25%) in men and women. After a low-calorie diet, combining aerobic exercise with liraglutide improved weight loss maintenance compared with either alone. Retaining lean mass during incretin therapy could blunt body weight (and fat) regain on cessation of weight loss pharmacotherapy. We propose that tailored resistance exercise training be recommended as an adjunct to incretin therapy to optimize changes in body composition by preserving lean mass while achieving fat loss.

Group-based behaviour therapy improves self-care, glycaemic control and distress in adults with type 1 diabetes.

AIMS: Psychological interventions have had modest effects on HbA1c in adults with Type 1 diabetes (T1D). We evaluated a novel behaviour therapy (BT) group program aiming to improve diabetes self-care and reduce HbA1c and distress. Core features were the application of a functional-analytic model, behavioural self-management training, and personally selected T1D self-care behaviours as treatment targets. METHODS: Participants with T1D, 2-consecutive HbA1c ≥ 8.5 %(69 mmol/mol) and/or diabetes-related emotional/behavioural difficulties who had received specialist multidisciplinary input for ≥2 years completed 6-sessions of BT over 9-weeks. Outcomes were assessed at baseline, on completing 5-consecutive weekly sessions (post-) and at session 6, 1-month after (follow-up). RESULTS: Of 66 participants mean age 37.9 years, mean age at T1D diagnosis 22.0 years, and median T1D duration 14 years, 54 completed BT. HbA1c improved from baseline to follow-up (9.7 ± 1.9 %-8.8 ± 1.3 %, p < 0.001), as did diabetes distress (DD: total score 49.2 ± 7.8 baseline, 38.9 ± 14.7 post- and 32.8 ± 11.7 follow-up, p < 0.001). All DD subscales of emotional burden, and physician, regimen, and interpersonal distress, improved (p < 0.001). Consistent results were observed for patients on multiple daily injections and continuous subcutaneous insulin infusion therapy. CONCLUSIONS: BT based on a functional-analytic and behavioural self-management model holds promise as an effective means of improving HbA1c and reducing DD in adults with T1D.

Early SGLT2 inhibitor use is associated with improved left atrial strain following acute coronary syndrome.

AIM: Left atrial (LA) strain, a novel marker of LA function, reliably predicts diastolic dysfunction. SGLT2 inhibitors improve heart failure outcomes, but limited data exists regarding their use in the immediate aftermath of acute coronary syndrome (ACS). We studied the effect of empagliflozin on LA strain in patients with type 2 diabetes (T2D) and ACS. METHODS: Patients with ACS and T2D were identified and empagliflozin was initiated in eligible patients prior to discharge. Patients not initiated on empagliflozin were analysed as a comparator group. A blinded investigator assessed LA strain using baseline and 3-6 month follow-up echocardiograms. RESULTS: Forty-four participants (n = 22 each group) were included. Baseline characteristics and LA strain were similar in the two groups. LA reservoir, conduit and contractile strain increased in empagliflozin group (28.0 ± 8.4% to 34.6 ± 12.2% p < 0.001, 14.5 ± 5.4% to 16.7 ± 7.0% p = 0.034, 13.5 ± 5.2% to 17.9 ± 7.2% p = 0.005, respectively) but remained unchanged in comparison group (29.2 ± 6.7% to 28.8 ± 7.0%, 12.8 ± 4.2% to 13.3 ± 4.7%, 16.7 ± 5.3% to 15.5 ± 4.5%, respectively, p = NS). The difference in change between groups was significant for LA reservoir (p = 0.003) and contractile strain (p = 0.005). CONCLUSION: In patients with ACS and T2D, addition of empagliflozin to standard ACS therapy prior to discharge is associated with improved LA function.

Patient perceptions of cardiovascular risk, lipid management and statins in type 1 diabetes.

Lipid-lowering reduces cardiovascular risk in type 1 diabetes (T1D), but dyslipidaemia remains under-recognised and under-treated. Through patient surveys, barriers to lipid management in T1D were identified, including lack of awareness of cardiovascular risk and cholesterol levels, preference for managing glycaemia over lipids, preference for lifestyle modification over pharmacotherapy, and statin side-effect concerns.